Work from the Aston-Jones lab in the last several years has established that noradrenergic locus coeruleus (LC) neurons in behaving monkeys exhibit different modes of impulse activity corresponding to different levels of performance in a discrimination task. These findings have led to the concept that the LC system regulation its target areas to favor either focused/stable vs. flexible. labile behavior. These studies have also revealed that IC impulse activity varies in close association with pupil diameter during this task, potentially offering a straightforward means of monitoring LC activity non-invasively for human studies. Finally, a variety of findings, including imaging studies by Cohen and colleagues, indicate that the anterior cingulate cortex (AC) may be integrally involved in determining the mode of LC activity. This project will test these hypotheses with a series of anatomical, physiological, and behavioral experiments in monkeys. Studies in Aim 1 will characterize the projections from the ACC to the LC. This is important to establish the corresponding anatomical pathway in primate relevant to the overall theme of his Center. Studies in Aim 2 will characterize the relationship between LC activity and pupil diameter, allowing an indirect index of LC activity via pupillary measures in humans in other projects. Finally, the proposed neurophysiological and microinjection behavioral studies (Aims 3 and 4) will test novel ideas concerning the role of the ACC and LC systems in regulating behavior in the face of conflict, a key concept for the Center overall. Together, these studies will establish the neurobiological basis in primates for the process investigated in psychological, modeling and imaging studies in other projects of this Center.